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Ivermectin and diethylcarbamazine (DEC) are used in mass treatment programs for the elimination of lymphatic filariasis because of their strong effects on microfilaremia. However, the effects of treatment on adult worms and the degree of individual variation in efficacy are unclear. We analyzed series of microfilaria (Mf) counts from individuals treated with a single dose of 400 μg/kg ivermectin or 6 mg/kg DEC (N = 23 in each group; 1 year follow-up). For each individual, we estimated the microfilaricidal effect and the reduction in overall Mf production (e.g., caused by death or sterilization of worms, or inhibited Mf release from the female worm uterus). Ivermectin on average killed 96% of Mf and reduced Mf production by 82%. DEC killed 57% of Mf and reduced Mf production by 67%, with some individuals responding very poorly. The strong reduction in overall Mf production is good news for control of lymphatic filariasis, but the prospects of elimination will be diminished if part of the population systematically responds poorly to treatment.